Low-molecular weight heparin is a bargain for VTE prevention.

Action Points

Note that this cost-effectiveness analysis of low-molecular weight heparin versus unfractionated heparin for thromboembolism prophylaxis in the ICU favored LMWH.

In fact, despite being the cheaper agent, there was no price point whereby unfractionated heparin would be the cost-effective agent.

Low-molecular weight heparin might be more cost-effective than unfractionated heparin for venous thromboembolism (VTE) prevention in critical illness, an international study showed.

Across five countries, hospital costs per patient were a median of $39,508 with dalteparin (Fragmin) compared with $40,805 on unfractionated heparin, Robert A. Fowler, MDCM, of the University of Toronto, and colleagues reported online in the Journal of the American Medical Association and at the Critical Care Canada Forum in Toronto.

"In this study, cost differences with LMWH were driven by apparent decreases in all thrombosis and heparin-induced thrombocytopenia and between-group differences in length of stay and accompanying resource use," Fowler's group noted.

Medication costs have historically been higher for LMWH, and "cost is cited as the most important barrier to using LMWH in a recent North American survey," they pointed out.

But "paying more may be worth it," based on the trial's findings altogether, the researchers suggested.

They projected that "if an ICU with 1,000 medical-surgical admissions per year uses unfractionated heparin instead of LMWH for prevention of VTE, the annual incremental cost may be between $1,000,000 to $1,500,000 with similar or worse clinical outcomes, despite the individual drug cost of unfractionated heparin being $4 to $5 less per day."

While the trial looked at a single LMWH, the findings likely would generalize to others, the group noted.

"... Existing observational evidence suggests a class effect for VTE prevention, and our threshold analysis indicates that even LMWHs with a higher drug acquisition cost are likely to represent an economically favorable strategy," they wrote.

In sensitivity analyses due to substantial drug acquisition cost variation across jurisdictions, LMWH remained less costly than unfractionated heparin unless the drug acquisition cost of dalteparin increased from $8 to $179 per dose.

"There was no threshold at which lowering the acquisition cost of unfractionated heparin favored prophylaxis with unfractionated heparin," Fowler and colleagues noted.

Fowler's prespecified analysis was done in the context of the randomized Prophylaxis for Thromboembolism in Critical Care (PROTECT) trial, which had shown no difference for the primary endpoint of leg deep vein thrombosis between the two treatments, although pulmonary embolism and heparin-induced thrombocytopenia were reduced with dalteparin.

Even when adjusting out that difference in pulmonary embolus risk between the two drugs, the median cost per patient remained lower with LMWH ($39,508 versus $40,633 with unfractionated heparin), indicating further cost savings.

The economic evaluation took a healthcare payer perspective and looked only at in-hospital outcomes and costs for the 2,344 medical-surgical ICU patients (76% medical) in the trial across 23 centers in the U.S., Canada, Australia, Saudi Arabia, and Brazil.

Costs were considered from patient-level, prospective data and included drugs, laboratory tests, personnel, diagnostic testing, procedures and operations, bleeding and blood product transfusion services, and infrastructure, all with international currency conversion.

Patients who got unfractionated heparin stayed in the hospital and in the ICU longer, which resulted in correspondingly higher personnel and fixed daily hospital costs.

The findings were consistent among higher- and lower-spending healthcare systems across the countries included and across subgroups by medical versus surgical status, illness severity, body mass index, and baseline use of vasopressors or inotropes. There were no country-specific differences in findings.

The protocolized ultrasounds for DVT included in the trial did not reflect usual practice, but were equal in number between groups and so did not impact differential costs, the researchers pointed out.

The American College of Chest Physicians and the British National Health Service (albeit both completed before publication of PROTECT) recommend either LMWH or unfractionated heparin for critically ill medical-surgical patients and recommend LMWH for those at highest risk of VTE, such as in orthopedic, neurosurgical, or pregnancy-related illness.

The lack of statistical significance in the main cost finding "may relate to limited power to demonstrate significant differences among only 23 centers," the researchers suggested.

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